1932

Abstract

Cellular immunotherapy holds great promise for the treatment of human disease. Clinical evidence suggests that T cell immunotherapies have the potential to combat cancers that evade traditional immunotherapy. Despite promising results, adverse effects leading to fatalities have left scientists seeking tighter control over these therapies, which is reflected in the growing body of synthetic biology literature focused on developing tightly controlled, context-independent parts. In addition, researchers are adapting these tools for other uses, such as for the treatment of autoimmune disease, HIV infection, and fungal interactions. We review this body of work and devote special attention to approaches that may lend themselves to the development of an “ideal” therapy: one that is safe, efficient, and easy to manufacture. We conclude with a look toward the future of immunotherapy: how synthetic biology can shift the paradigm from the treatment of disease to a focus on wellness and human health as a whole.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-bioeng-062117-121147
2018-06-04
2024-04-12
Loading full text...

Full text loading...

/deliver/fulltext/20/1/annurev-bioeng-062117-121147.html?itemId=/content/journals/10.1146/annurev-bioeng-062117-121147&mimeType=html&fmt=ahah

Literature Cited

  1. 1.  Pardoll DM 2012. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 12:252–64
    [Google Scholar]
  2. 2.  Van Allen EM, Miao D, Schilling B, Shukla SA, Blank C et al. 2015. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 350:207–11
    [Google Scholar]
  3. 3.  McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R et al. 2016. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 351:1463–69
    [Google Scholar]
  4. 4.  Rapoport AP, Stadtmauer EA, Binder-Scholl GK, Goloubeva O, Vogl DT et al. 2015. NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat. Med. 21:914–21
    [Google Scholar]
  5. 5.  Sadelain M, Brentjens R, Rivière I 2013. The basic principles of chimeric antigen receptor design. Cancer Discov 3:388–98
    [Google Scholar]
  6. 6.  Porter DL, Levine BL, Kalos M, Bagg A, June CH 2011. Chimeric antigen receptor–modified T cells in chronic lymphoid leukemia. N. Engl. J. Med. 365:725–33
    [Google Scholar]
  7. 7.  Davila ML, Rivière I, Wang X, Bartido S, Park J et al. 2014. Efficacy and toxicity management of 19–28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci. Transl. Med. 6:224ra25
    [Google Scholar]
  8. 8.  Gardner TS, Cantor CR, Collins JJ 2000. Construction of a genetic toggle switch in Escherichia coli. . Nature 403:339–42
    [Google Scholar]
  9. 9.  Elowitz MB, Leibler S 2000. A synthetic oscillatory network of transcriptional regulators. Nature 403:335–38
    [Google Scholar]
  10. 10.  Mondragon-Palomino O, Danino T, Selimkhanov J, Tsimring L, Hasty J 2011. Entrainment of a population of synthetic genetic oscillators. Science 333:1315–19
    [Google Scholar]
  11. 11.  Weinberg BH, Pham NTH, Caraballo LD, Lozanoski T, Engel A et al. 2017. Large-scale design of robust genetic circuits with multiple inputs and outputs for mammalian cells. Nat. Biotechnol. 35:453–62
    [Google Scholar]
  12. 12.  Siuti P, Yazbek J, Lu TK 2013. Synthetic circuits integrating logic and memory in living cells. Nat. Biotechnol. 31:448–52
    [Google Scholar]
  13. 13.  Guinn M, Bleris L 2014. Biological 2-input decoder circuit in human cells. ACS Synth. Biol. 3:627–33
    [Google Scholar]
  14. 14.  Wei P, Wong WW, Park JS, Corcoran EE, Peisajovich SG et al. 2012. Bacterial virulence proteins as tools to rewire kinase pathways in yeast and immune cells. Nature 488:384–88
    [Google Scholar]
  15. 15.  Becskei A, Serrano L 2000. Engineering stability in gene networks by autoregulation. Nature 405:590–93
    [Google Scholar]
  16. 16.  Xie M, Ye H, Wang H, Charpin-El Hamri G, Lormeau C et al. 2016. β-cell-mimetic designer cells provide closed-loop glycemic control. Science 354:1296–301
    [Google Scholar]
  17. 17.  Atsumi S, Hanai T, Liao JC 2008. Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels. Nature 451:86–89
    [Google Scholar]
  18. 18.  Ro DK, Paradise EM, Ouellet M, Fisher KJ, Newman KL et al. 2006. Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440:940–43
    [Google Scholar]
  19. 19.  DeLoache WC, Russ ZN, Narcross L, Gonzales AM, Martin VJ, Dueber JE 2015. An enzyme-coupled biosensor enables (S)-reticuline production in yeast from glucose. Nat. Chem. Biol. 11:465–71
    [Google Scholar]
  20. 20.  Galanie S, Thodey K, Trenchard IJ, Filsinger Interrante M, Smolke CD 2015. Complete biosynthesis of opioids in yeast. Science 349:1095–100
    [Google Scholar]
  21. 21.  Ajikumar PK, Xiao WH, Tyo KE, Wang Y, Simeon F et al. 2010. Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli. . Science 330:70–74
    [Google Scholar]
  22. 22.  Yim H, Haselbeck R, Niu W, Pujol-Baxley C, Burgard A et al. 2011. Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol. Nat. Chem. Biol. 7:445–52
    [Google Scholar]
  23. 23.  Choi SY, Park SJ, Kim WJ, Yang JE, Lee H et al. 2016. One-step fermentative production of poly(lactate-co-glycolate) from carbohydrates in Escherichia coli. . Nat. Biotechnol. 34:435–40
    [Google Scholar]
  24. 24.  Chappell J, Takahashi MK, Lucks JB 2015. Creating small transcription activating RNAs. Nat. Chem. Biol. 11:214–20
    [Google Scholar]
  25. 25.  Green AA, Silver PA, Collins JJ, Yin P 2014. Toehold switches: de-novo-designed regulators of gene expression. Cell 159:925–39
    [Google Scholar]
  26. 26.  Bonnet J, Yin P, Ortiz ME, Subsoontorn P, Endy D 2013. Amplifying genetic logic gates. Science 340:599–603
    [Google Scholar]
  27. 27.  Khalil AS, Lu TK, Bashor CJ, Ramirez CL, Pyenson NC et al. 2012. A synthetic biology framework for programming eukaryotic transcription functions. Cell 150:647–58
    [Google Scholar]
  28. 28.  Schwarz KA, Daringer NM, Dolberg TB, Leonard JN 2017. Rewiring human cellular input-output using modular extracellular sensors. Nat. Chem. Biol. 13:202–9
    [Google Scholar]
  29. 29.  Morsut L, Roybal KT, Xiong X, Gordley RM, Coyle SM et al. 2016. Engineering customized cell sensing and response behaviors using synthetic Notch receptors. Cell 164:780–91
    [Google Scholar]
  30. 30.  Gibson DG, Young L, Chuang RY, Venter JC, Hutchison CA3rd, Smith HO 2009. Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat. Methods 6:343–45
    [Google Scholar]
  31. 31.  Weber E, Engler C, Gruetzner R, Werner S, Marillonnet S 2011. A modular cloning system for standardized assembly of multigene constructs. PLOS ONE 6:e16765
    [Google Scholar]
  32. 32.  Kong DS, Thorsen TA, Babb J, Wick ST, Gam JJ et al. 2017. Open-source, community-driven microfluidics with Metafluidics. Nat. Biotechnol. 35:523–29
    [Google Scholar]
  33. 33.  Gaj T, Gersbach CA, Barbas CF3rd 2013. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol 31:397–405
    [Google Scholar]
  34. 34.  Woodsworth DJ, Holt RA 2017. Cell-based therapeutics: making a Faustian pact with biology. Trends Mol. Med. 23:104–15
    [Google Scholar]
  35. 35.  Nielsen AA, Der BS, Shin J, Vaidyanathan P, Paralanov V et al. 2016. Genetic circuit design automation. Science 352:aac7341
    [Google Scholar]
  36. 36.  Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL et al. 1988. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N. Engl. J. Med. 319:1676–80
    [Google Scholar]
  37. 37.  Kershaw MH, Westwood JA, Parker LL, Wang G, Eshhar Z et al. 2006. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin. Cancer Res. 12:6106–15
    [Google Scholar]
  38. 38.  Kowolik CM, Topp MS, Gonzalez S, Pfeiffer T, Olivares S et al. 2006. CD28 costimulation provided through a CD19-specific chimeric antigen receptor enhances in vivo persistence and antitumor efficacy of adoptively transferred T cells. Cancer Res 66:10995–1004
    [Google Scholar]
  39. 39.  Wang J, Jensen M, Lin Y, Sui X, Chen E et al. 2007. Optimizing adoptive polyclonal T cell immunotherapy of lymphomas, using a chimeric T cell receptor possessing CD28 and CD137 costimulatory domains. Hum. Gene Ther. 18:712–25
    [Google Scholar]
  40. 40.  Kochenderfer JN, Dudley ME, Feldman SA, Wilson WH, Spaner DE et al. 2012. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood 119:2709–20
    [Google Scholar]
  41. 41.  Brentjens R, Yeh R, Bernal Y, Rivière I, Sadelain M 2010. Treatment of chronic lymphocytic leukemia with genetically targeted autologous T cells: case report of an unforeseen adverse event in a phase I clinical trial. Mol. Ther. 18:666–68
    [Google Scholar]
  42. 42.  Sadelain M, Rivière I, Riddell S 2017. Therapeutic T cell engineering. Nature 545:423–31
    [Google Scholar]
  43. 43.  Lim WA, June CH 2017. The principles of engineering immune cells to treat cancer. Cell 168:724–40
    [Google Scholar]
  44. 44.  Roberts MR, Qin L, Zhang D, Smith DH, Tran AC et al. 1994. Targeting of human immunodeficiency virus–infected cells by CD8+ T lymphocytes armed with universal T-cell receptors. Blood 84:2878–89
    [Google Scholar]
  45. 45.  Deeks SG, Wagner B, Anton PA, Mitsuyasu RT, Scadden DT et al. 2002. A phase II randomized study of HIV-specific T-cell gene therapy in subjects with undetectable plasma viremia on combination antiretroviral therapy. Mol. Ther. 5:788–97
    [Google Scholar]
  46. 46.  Scholler J, Brady TL, Binder-Scholl G, Hwang WT, Plesa G et al. 2012. Decade-long safety and function of retroviral-modified chimeric antigen receptor T cells. Sci. Transl. Med. 4:132ra53
    [Google Scholar]
  47. 47.  Liu B, Zou F, Lu L, Chen C, He D et al. 2016. Chimeric antigen receptor T cells guided by the single-chain Fv of a broadly neutralizing antibody specifically and effectively eradicate virus reactivated from latency in CD4+ T lymphocytes isolated from HIV-1-infected individuals receiving suppressive combined antiretroviral therapy. J. Virol. 90:9712–24
    [Google Scholar]
  48. 48.  Ali A, Kitchen SG, Chen IS, Ng HL, Zack JA, Yang OO 2016. HIV-1-specific chimeric antigen receptors based on broadly neutralizing antibodies. J. Virol. 90:6999–7006
    [Google Scholar]
  49. 49.  Hale M, Mesojednik T, Romano Ibarra GS, Sahni J, Bernard A et al. 2017. Engineering HIV-resistant, anti-HIV chimeric antigen receptor T cells. Mol. Ther. 25:570–79
    [Google Scholar]
  50. 50.  Descours B, Petitjean G, López-Zaragoza JL, Bruel T, Raffel R et al. 2017. CD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses. Nature 543:564–67
    [Google Scholar]
  51. 51.  Kriengkauykiat J, Ito JI, Dadwal SS 2011. Epidemiology and treatment approaches in management of invasive fungal infections. Clin. Epidemiol. 3:175–91
    [Google Scholar]
  52. 52.  Armstrong-James D, Harrison TS 2012. Immunotherapy for fungal infections. Curr. Opin. Microbiol. 15:434–39
    [Google Scholar]
  53. 53.  Armstrong-James D, Teo IA, Shrivastava S, Petrou MA, Taube D et al. 2010. Exogenous interferon-γ immunotherapy for invasive fungal infections in kidney transplant patients. Am. J. Transplant. 10:1796–803
    [Google Scholar]
  54. 54.  Safdar A, Rodriguez G, Ohmagari N, Kontoyiannis DP, Rolston KV et al. 2005. The safety of interferon-γ-1b therapy for invasive fungal infections after hematopoietic stem cell transplantation. Cancer 103:731–39
    [Google Scholar]
  55. 55.  Jarvis JN, Meintjes G, Rebe K, Williams GN, Bicanic T et al. 2012. Adjunctive interferon-γ immunotherapy for the treatment of HIV-associated cryptococcal meningitis: a randomized controlled trial. AIDS 26:1105–13
    [Google Scholar]
  56. 56.  Cowen LE, Singh SD, Kohler JR, Collins C, Zaas AK et al. 2009. Harnessing Hsp90 function as a powerful, broadly effective therapeutic strategy for fungal infectious disease. PNAS 106:2818–23
    [Google Scholar]
  57. 57.  Bryan RA, Jiang Z, Howell RC, Morgenstern A, Bruchertseifer F et al. 2010. Radioimmunotherapy is more effective than antifungal treatment in experimental cryptococcal infection. J. Infect. Dis. 202:633–37
    [Google Scholar]
  58. 58.  Louie A, Stein DS, Zack JZ, Liu W, Conde H et al. 2011. Dose range evaluation of Mycograb C28Y variant, a human recombinant antibody fragment to heat shock protein 90, in combination with amphotericin B–desoxycholate for treatment of murine systemic candidiasis. Antimicrob. Agents Chemother. 55:3295–304
    [Google Scholar]
  59. 59.  Bozza S, Perruccio K, Montagnoli C, Gaziano R, Bellocchio S et al. 2003. A dendritic cell vaccine against invasive aspergillosis in allogeneic hematopoietic transplantation. Blood 102:3807–14
    [Google Scholar]
  60. 60.  Ang AL, Linn YC 2011. Treatment of severe neutropenic sepsis with granulocyte transfusion in the current era—experience from an adult haematology unit in Singapore. Transfus. Med. 21:13–24
    [Google Scholar]
  61. 61.  Safdar A, Hanna HA, Boktour M, Kontoyiannis DP, Hachem R et al. 2004. Impact of high-dose granulocyte transfusions in patients with cancer with candidemia: retrospective case-control analysis of 491 episodes of Candida species bloodstream infections. Cancer 101:2859–65
    [Google Scholar]
  62. 62.  Lin L, Ibrahim AS, Baquir B, Fu Y, Applebaum D et al. 2010. Safety and efficacy of activated transfected killer cells for neutropenic fungal infections. J. Infect. Dis. 201:1708–17
    [Google Scholar]
  63. 63.  Perruccio K, Tosti A, Burchielli E, Topini F, Ruggeri L et al. 2005. Transferring functional immune responses to pathogens after haploidentical hematopoietic transplantation. Blood 106:4397–406
    [Google Scholar]
  64. 64.  Gaundar SS, Clancy L, Blyth E, Meyer W, Gottlieb DJ 2012. Robust polyfunctional T-helper 1 responses to multiple fungal antigens from a cell population generated using an environmental strain of Aspergillus fumigatus. . Cytotherapy 14:1119–30
    [Google Scholar]
  65. 65.  Bacher P, Jochheim-Richter A, Mockel-Tenbrink N, Kniemeyer O, Wingenfeld E et al. 2015. Clinical-scale isolation of the total Aspergillus fumigatus–reactive T-helper cell repertoire for adoptive transfer. Cytotherapy 17:1396–405
    [Google Scholar]
  66. 66.  Papadopoulou A, Kaloyannidis P, Yannaki E, Cruz CR 2016. Adoptive transfer of Aspergillus-specific T cells as a novel anti-fungal therapy for hematopoietic stem cell transplant recipients: progress and challenges. Crit. Rev. Oncol. Hematol. 98:62–72
    [Google Scholar]
  67. 67.  Kumaresan PR, Manuri PR, Albert ND, Maiti S, Singh H et al. 2014. Bioengineering T cells to target carbohydrate to treat opportunistic fungal infection. PNAS 111:10660–65
    [Google Scholar]
  68. 68.  Parida SK, Poiret T, Zhenjiang L, Meng Q, Heyckendorf J et al. 2015. T-cell therapy: options for infectious diseases. Clin. Infect. Dis. 61:Suppl. 3S217–24
    [Google Scholar]
  69. 69.  Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P et al. 2004. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N. Engl. J. Med. 350:2572–81
    [Google Scholar]
  70. 70.  Tchorbanov AI, Voynova EN, Mihaylova NM, Todorov TA, Nikolova M et al. 2007. Selective silencing of DNA-specific B lymphocytes delays lupus activity in MRL/lpr mice. Eur. J. Immunol. 37:3587–96
    [Google Scholar]
  71. 71.  Ellebrecht CT, Bhoj VG, Nace A, Choi EJ, Mao X et al. 2016. Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease. Science 353:179–84
    [Google Scholar]
  72. 72.  Elinav E, Adam N, Waks T, Eshhar Z 2009. Amelioration of colitis by genetically engineered murine regulatory T cells redirected by antigen-specific chimeric receptor. Gastroenterology 136:1721–31
    [Google Scholar]
  73. 73.  Taylor PA, Lees CJ, Blazar BR 2002. The infusion of ex vivo activated and expanded CD4+CD25+ immune regulatory cells inhibits graft-versus-host disease lethality. Blood 99:3493–99
    [Google Scholar]
  74. 74.  MacDonald KG, Hoeppli RE, Huang Q, Gillies J, Luciani DS et al. 2016. Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor. J. Clin. Investig. 126:1413–24
    [Google Scholar]
  75. 75.  Gornalusse GG, Hirata RK, Funk SE, Riolobos L, Lopes VS et al. 2017. HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells. Nat. Biotechnol. 35:765–72
    [Google Scholar]
  76. 76.  Kim YC, Zhang AH, Su Y, Rieder SA, Rossi RJ et al. 2015. Engineered antigen-specific human regulatory T cells: immunosuppression of FVIII-specific T- and B-cell responses. Blood 125:1107–15
    [Google Scholar]
  77. 77.  Yoon J, Schmidt A, Zhang AH, Konigs C, Kim YC, Scott DW 2017. FVIII-specific human chimeric antigen receptor T-regulatory cells suppress T- and B-cell responses to FVIII. Blood 129:238–45
    [Google Scholar]
  78. 78.  McLaughlin KA, Richardson CC, Ravishankar A, Brigatti C, Liberati D et al. 2016. Identification of tetraspanin-7 as a target of autoantibodies in type 1 diabetes. Diabetes 65:1690–98
    [Google Scholar]
  79. 79.  Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA 2010. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol. Ther. 18:843–51
    [Google Scholar]
  80. 80.  Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C et al. 2015. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 385:517–28
    [Google Scholar]
  81. 81.  Morgan RA, Chinnasamy N, Abate-Daga D, Gros A, Robbins PF et al. 2013. Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J. Immunother. 36:133–51
    [Google Scholar]
  82. 82.  Deo SS, Gottlieb DJ 2015. Adoptive T-cell therapy for fungal infections in haematology patients. Clin. Transl. Immunol. 4:e40
    [Google Scholar]
  83. 83.  Liu L, Patel B, Ghanem MH, Bundoc V, Zheng Z et al. 2015. Novel CD4-based bispecific chimeric antigen receptor designed for enhanced anti-HIV potency and absence of HIV entry receptor activity. J. Virol. 89:6685–94
    [Google Scholar]
  84. 84.  Delfortrie S, Pinte S, Mattot V, Samson C, Villain G et al. 2011. Egfl7 promotes tumor escape from immunity by repressing endothelial cell activation. Cancer Res 71:7176–86
    [Google Scholar]
  85. 85.  Firth JD, Ebert BL, Pugh CW, Ratcliffe PJ 1994. Oxygen-regulated control elements in the phosphoglycerate kinase 1 and lactate dehydrogenase A genes: similarities with the erythropoietin 3′ enhancer. PNAS 91:6496–500
    [Google Scholar]
  86. 86.  Ohta A, Gorelik E, Prasad SJ, Ronchese F, Lukashev D et al. 2006. A2A adenosine receptor protects tumors from antitumor T cells. PNAS 103:13132–37
    [Google Scholar]
  87. 87.  Waickman AT, Alme A, Senaldi L, Zarek PE, Horton M, Powell JD 2012. Enhancement of tumor immunotherapy by deletion of the A2A adenosine receptor. Cancer Immunol. Immunother. 61:917–26
    [Google Scholar]
  88. 88.  Scharping NE, Menk AV, Moreci RS, Whetstone RD, Dadey RE et al. 2016. The tumor microenvironment represses T cell mitochondrial biogenesis to drive intratumoral T cell metabolic insufficiency and dysfunction. Immunity 45:374–88
    [Google Scholar]
  89. 89.  Coussens LM, Werb Z 2002. Inflammation and cancer. Nature 420:860–67
    [Google Scholar]
  90. 90.  Torroella-Kouri M, Silvera R, Rodriguez D, Caso R, Shatry A et al. 2009. Identification of a subpopulation of macrophages in mammary tumor–bearing mice that are neither M1 nor M2 and are less differentiated. Cancer Res 69:4800–9
    [Google Scholar]
  91. 91.  DeNardo DG, Brennan DJ, Rexhepaj E, Ruffell B, Shiao SL et al. 2011. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov 1:54–67
    [Google Scholar]
  92. 92.  Chen X, Takemoto Y, Deng H, Middelhoff M, Friedman RA et al. 2017. Histidine decarboxylase (HDC)-expressing granulocytic myeloid cells induce and recruit Foxp3+ regulatory T cells in murine colon cancer. Oncoimmunology 6:e1290034
    [Google Scholar]
  93. 93.  Bates GJ, Fox SB, Han C, Leek RD, Garcia JF et al. 2006. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J. Clin. Oncol. 24:5373–80
    [Google Scholar]
  94. 94.  Wang X, Rivière I 2016. Clinical manufacturing of CAR T cells: foundation of a promising therapy. Mol. Ther. Oncolytics 3:16015
    [Google Scholar]
  95. 95.  Lienert F, Lohmueller JJ, Garg A, Silver PA 2014. Synthetic biology in mammalian cells: next generation research tools and therapeutics. Nat. Rev. Mol. Cell Biol. 15:95–107
    [Google Scholar]
  96. 96.  Rinaudo K, Bleris L, Maddamsetti R, Subramanian S, Weiss R, Benenson Y 2007. A universal RNAi-based logic evaluator that operates in mammalian cells. Nat. Biotechnol. 25:795–801
    [Google Scholar]
  97. 97.  Xie Z, Liu SJ, Bleris L, Benenson Y 2010. Logic integration of mRNA signals by an RNAi-based molecular computer. Nucleic Acids Res 38:2692–701
    [Google Scholar]
  98. 98.  Nishimura K, Fukagawa T, Takisawa H, Kakimoto T, Kanemaki M 2009. An auxin-based degron system for the rapid depletion of proteins in nonplant cells. Nat. Methods 6:917–22
    [Google Scholar]
  99. 99.  Chung HK, Jacobs CL, Huo Y, Yang J, Krumm SA et al. 2015. Tunable and reversible drug control of protein production via a self-excising degron. Nat. Chem. Biol. 11:713–20
    [Google Scholar]
  100. 100.  Grimley JS, Chen DA, Banaszynski LA, Wandless TJ 2008. Synthesis and analysis of stabilizing ligands for FKBP-derived destabilizing domains. Bioorg. Med. Chem. Lett. 18:759–61
    [Google Scholar]
  101. 101.  Wu CY, Roybal KT, Puchner EM, Onuffer J, Lim WA 2015. Remote control of therapeutic T cells through a small molecule-gated chimeric receptor. Science 350:aab4077
    [Google Scholar]
  102. 102.  Miyamoto T, DeRose R, Suarez A, Ueno T, Chen M et al. 2012. Rapid and orthogonal logic gating with a gibberellin-induced dimerization system. Nat. Chem. Biol. 8:465–70
    [Google Scholar]
  103. 103.  Taslimi A, Zoltowski B, Miranda JG, Pathak GP, Hughes RM, Tucker CL 2016. Optimized second-generation CRY2-CIB dimerizers and photoactivatable Cre recombinase. Nat. Chem. Biol. 12:425–30
    [Google Scholar]
  104. 104.  Inoue T, Heo WD, Grimley JS, Wandless TJ, Meyer T 2005. An inducible translocation strategy to rapidly activate and inhibit small GTPase signaling pathways. Nat. Methods 2:415–18
    [Google Scholar]
  105. 105.  Levskaya A, Weiner OD, Lim WA, Voigt CA 2009. Spatiotemporal control of cell signalling using a light-switchable protein interaction. Nature 461:997–1001
    [Google Scholar]
  106. 106.  Polstein LR, Gersbach CA 2015. A light-inducible CRISPR-Cas9 system for control of endogenous gene activation. Nat. Chem. Biol. 11:198–200
    [Google Scholar]
  107. 107.  Niopek D, Benzinger D, Roensch J, Draebing T, Wehler P et al. 2014. Engineering light-inducible nuclear localization signals for precise spatiotemporal control of protein dynamics in living cells. Nat. Commun. 5:4404
    [Google Scholar]
  108. 108.  Guntas G, Hallett RA, Zimmerman SP, Williams T, Yumerefendi H et al. 2015. Engineering an improved light-induced dimer (iLID) for controlling the localization and activity of signaling proteins. PNAS 112:112–17
    [Google Scholar]
  109. 109.  Gossen M, Bujard H 1992. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. PNAS 89:5547–51
    [Google Scholar]
  110. 110.  Brown M, Figge J, Hansen U, Wright C, Jeang KT et al. 1987. lac repressor can regulate expression from a hybrid SV40 early promoter containing a lac operator in animal cells. Cell 49:603–12
    [Google Scholar]
  111. 111.  Maeder ML, Thibodeau-Beganny S, Osiak A, Wright DA, Anthony RM et al. 2008. Rapid “open-source” engineering of customized zinc-finger nucleases for highly efficient gene modification. Mol. Cell 31:294–301
    [Google Scholar]
  112. 112.  Keung AJ, Bashor CJ, Kiriakov S, Collins JJ, Khalil AS 2014. Using targeted chromatin regulators to engineer combinatorial and spatial transcriptional regulation. Cell 158:110–20
    [Google Scholar]
  113. 113.  Morbitzer R, Romer P, Boch J, Lahaye T 2010. Regulation of selected genome loci using de novo–engineered transcription activator–like effector (TALE)-type transcription factors. PNAS 107:21617–22
    [Google Scholar]
  114. 114.  Garg A, Lohmueller JJ, Silver PA, Armel TZ 2012. Engineering synthetic TAL effectors with orthogonal target sites. Nucleic Acids Res 40:7584–95
    [Google Scholar]
  115. 115.  Reyon D, Khayter C, Regan MR, Joung JK, Sander JD 2012. Engineering designer transcription activator-like effector nucleases (TALENs) by REAL or REAL-Fast assembly. Curr. Protoc. Mol. Biol. 100:12.15.1–12.15.14
    [Google Scholar]
  116. 116.  Qi LS, Larson MH, Gilbert LA, Doudna JA, Weissman JS et al. 2013. Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell 152:1173–83
    [Google Scholar]
  117. 117.  Maeder ML, Linder SJ, Cascio VM, Fu Y, Ho QH, Joung JK 2013. CRISPR RNA-guided activation of endogenous human genes. Nat. Methods 10:977–79
    [Google Scholar]
  118. 118.  Perez-Pinera P, Kocak DD, Vockley CM, Adler AF, Kabadi AM et al. 2013. RNA-guided gene activation by CRISPR-Cas9-based transcription factors. Nat. Methods 10:973–76
    [Google Scholar]
  119. 119.  Jinek M, East A, Cheng A, Lin S, Ma E, Doudna J 2013. RNA-programmed genome editing in human cells. eLife 2:e00471
    [Google Scholar]
  120. 120.  Bibikova M, Beumer K, Trautman JK, Carroll D 2003. Enhancing gene targeting with designed zinc finger nucleases. Science 300:764
    [Google Scholar]
  121. 121.  Eyquem J, Mansilla-Soto J, Giavridis T, van der Stegen SJ, Hamieh M et al. 2017. Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature 543:113–17
    [Google Scholar]
  122. 122.  Conklin BR, Hsiao EC, Claeysen S, Dumuis A, Srinivasan S et al. 2008. Engineering GPCR signaling pathways with RASSLs. Nat. Methods 5:673–78
    [Google Scholar]
  123. 123.  Barnea G, Strapps W, Herrada G, Berman Y, Ong J et al. 2008. The genetic design of signaling cascades to record receptor activation. PNAS 105:64–69
    [Google Scholar]
  124. 124.  Roybal KT, Williams JZ, Morsut L, Rupp LJ, Kolinko I et al. 2016. Engineering T cells with customized therapeutic response programs using synthetic Notch receptors. Cell 167:419–32
    [Google Scholar]
  125. 125.  Roybal KT, Rupp LJ, Morsut L, Walker WJ, McNally KA et al. 2016. Precision tumor recognition by T cells with combinatorial antigen-sensing circuits. Cell 164:770–79
    [Google Scholar]
  126. 126.  Hegde M, Corder A, Chow KK, Mukherjee M, Ashoori A et al. 2013. Combinational targeting offsets antigen escape and enhances effector functions of adoptively transferred T cells in glioblastoma. Mol. Ther. 21:2087–101
    [Google Scholar]
  127. 127.  Grada Z, Hegde M, Byrd T, Shaffer DR, Ghazi A et al. 2013. TanCAR: a novel bispecific chimeric antigen receptor for cancer immunotherapy. Mol. Ther. Nucleic Acids 2:e105
    [Google Scholar]
  128. 128.  Wu CY, Rupp LJ, Roybal KT, Lim WA 2015. Synthetic biology approaches to engineer T cells. Curr. Opin. Immunol. 35:123–30
    [Google Scholar]
  129. 129.  Rodgers DT, Mazagova M, Hampton EN, Cao Y, Ramadoss NS et al. 2016. Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies. PNAS 113:E459–68
    [Google Scholar]
  130. 130.  Ma JS, Kim JY, Kazane SA, Choi SH, Yun HY et al. 2016. Versatile strategy for controlling the specificity and activity of engineered T cells. PNAS 113:E450–58
    [Google Scholar]
  131. 131.  Tamada K, Geng D, Sakoda Y, Bansal N, Srivastava R et al. 2012. Redirecting gene-modified T cells toward various cancer types using tagged antibodies. Clin. Cancer Res. 18:6436–45
    [Google Scholar]
  132. 132.  Urbanska K, Lanitis E, Poussin M, Lynn RC, Gavin BP et al. 2012. A universal strategy for adoptive immunotherapy of cancer through use of a novel T-cell antigen receptor. Cancer Res 72:1844–52
    [Google Scholar]
  133. 133.  Fedorov VD, Themeli M, Sadelain M 2013. PD-1- and CTLA-4-based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses. Sci. Transl. Med. 5:215ra172
    [Google Scholar]
  134. 134.  Di Stasi A, Tey SK, Dotti G, Fujita Y, Kennedy-Nasser A et al. 2011. Inducible apoptosis as a safety switch for adoptive cell therapy. N. Engl. J. Med. 365:1673–83
    [Google Scholar]
  135. 135.  Straathof KC, Pule MA, Yotnda P, Dotti G, Vanin EF et al. 2005. An inducible caspase 9 safety switch for T-cell therapy. Blood 105:4247–54
    [Google Scholar]
  136. 136.  Peng W, Ye Y, Rabinovich BA, Liu C, Lou Y et al. 2010. Transduction of tumor-specific T cells with CXCR2 chemokine receptor improves migration to tumor and antitumor immune responses. Clin. Cancer Res. 16:5458–68
    [Google Scholar]
  137. 137.  Moon EK, Carpenito C, Sun J, Wang LC, Kapoor V et al. 2011. Expression of a functional CCR2 receptor enhances tumor localization and tumor eradication by retargeted human T cells expressing a mesothelin-specific chimeric antibody receptor. Clin. Cancer Res. 17:4719–30
    [Google Scholar]
  138. 138.  Xu Y, Hyun YM, Lim K, Lee H, Cummings RJ et al. 2014. Optogenetic control of chemokine receptor signal and T-cell migration. PNAS 111:6371–76
    [Google Scholar]
  139. 139.  Caruana I, Savoldo B, Hoyos V, Weber G, Liu H et al. 2015. Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes. Nat. Med. 21:524–29
    [Google Scholar]
  140. 140.  Zhang L, Yu Z, Muranski P, Palmer DC, Restifo NP et al. 2013. Inhibition of TGF-β signaling in genetically engineered tumor antigen–reactive T cells significantly enhances tumor treatment efficacy. Gene Ther 20:575–80
    [Google Scholar]
  141. 141.  Leen AM, Sukumaran S, Watanabe N, Mohammed S, Keirnan J et al. 2014. Reversal of tumor immune inhibition using a chimeric cytokine receptor. Mol. Ther. 22:1211–20
    [Google Scholar]
  142. 142.  Prosser ME, Brown CE, Shami AF, Forman SJ, Jensen MC 2012. Tumor PD-L1 co-stimulates primary human CD8+ cytotoxic T cells modified to express a PD1:CD28 chimeric receptor. Mol. Immunol. 51:263–72
    [Google Scholar]
  143. 143.  Komita H, Zhao X, Katakam AK, Kumar P, Kawabe M et al. 2009. Conditional interleukin-12 gene therapy promotes safe and effective antitumor immunity. Cancer Gene Ther 16:883–91
    [Google Scholar]
  144. 144.  Zhang L, Morgan RA, Beane JD, Zheng Z, Dudley ME et al. 2015. Tumor-infiltrating lymphocytes genetically engineered with an inducible gene encoding interleukin-12 for the immunotherapy of metastatic melanoma. Clin. Cancer Res. 21:2278–88
    [Google Scholar]
  145. 145.  Qasim W, Zhan H, Samarasinghe S, Adams S, Amrolia P et al. 2017. Molecular remission of infant B-ALL after infusion of universal TALEN gene–edited CAR T cells. Sci. Transl. Med. 9:eaaj2013
    [Google Scholar]
  146. 146.  Liu L, Sommermeyer D, Cabanov A, Kosasih P, Hill T, Riddell SR 2016. Inclusion of Strep-tag II in design of antigen receptors for T-cell immunotherapy. Nat. Biotechnol. 34:430–34
    [Google Scholar]
  147. 147.  Kwong GA, von Maltzahn G, Murugappan G, Abudayyeh O, Mo S et al. 2013. Mass-encoded synthetic biomarkers for multiplexed urinary monitoring of disease. Nat. Biotechnol. 31:63–70
    [Google Scholar]
  148. 148.  Kwon EJ, Dudani JS, Bhatia SN 2017. Ultrasensitive tumour-penetrating nanosensors of protease activity. Nat. Biomed. Eng. 1:0054
    [Google Scholar]
  149. 149.  Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ et al. 2016. Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature 530:184–89
    [Google Scholar]
  150. 150.  Chang J, Wang Y, Shao L, Laberge RM, Demaria M et al. 2016. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat. Med. 22:78–83
    [Google Scholar]
/content/journals/10.1146/annurev-bioeng-062117-121147
Loading
/content/journals/10.1146/annurev-bioeng-062117-121147
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error